No effect of acute tryptophan depletion on phosphodiesterase inhibition-related improvements of short-term object memory in male Wistar rats

E.L. van Donkelaar, J. Prickaerts, S. Akkerman, K. Rutten, Harry Steinbusch, A. Blokland

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

ObjectiveTo further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD). MethodWistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance. ResultsAlthough ATD significantly decreased TRP levels in the hippocampus 2h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed. ConclusionChanges in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.
Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalActa Psychiatrica Scandinavica
Volume128
Issue number2
DOIs
Publication statusPublished - Aug 2013

Keywords

  • phosphodiesterase inhibitors
  • acute tryptophan depletion
  • serotonin
  • rat object memory
  • CEREBRAL-BLOOD-FLOW
  • GELATIN-BASED MIXTURE
  • NITRIC-OXIDE SYNTHASE
  • AFFECTIVE BEHAVIOR
  • SEROTONIN RELEASE
  • AMINO-ACIDS
  • BRAIN
  • DOPAMINE
  • CGMP
  • NORADRENALINE

Cite this

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title = "No effect of acute tryptophan depletion on phosphodiesterase inhibition-related improvements of short-term object memory in male Wistar rats",
abstract = "ObjectiveTo further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD). MethodWistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance. ResultsAlthough ATD significantly decreased TRP levels in the hippocampus 2h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed. ConclusionChanges in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.",
keywords = "phosphodiesterase inhibitors, acute tryptophan depletion, serotonin, rat object memory, CEREBRAL-BLOOD-FLOW, GELATIN-BASED MIXTURE, NITRIC-OXIDE SYNTHASE, AFFECTIVE BEHAVIOR, SEROTONIN RELEASE, AMINO-ACIDS, BRAIN, DOPAMINE, CGMP, NORADRENALINE",
author = "{van Donkelaar}, E.L. and J. Prickaerts and S. Akkerman and K. Rutten and Harry Steinbusch and A. Blokland",
year = "2013",
month = "8",
doi = "10.1111/acps.12166",
language = "English",
volume = "128",
pages = "107--113",
journal = "Acta Psychiatrica Scandinavica",
issn = "0001-690X",
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No effect of acute tryptophan depletion on phosphodiesterase inhibition-related improvements of short-term object memory in male Wistar rats. / van Donkelaar, E.L.; Prickaerts, J.; Akkerman, S.; Rutten, K.; Steinbusch, Harry; Blokland, A.

In: Acta Psychiatrica Scandinavica, Vol. 128, No. 2, 08.2013, p. 107-113.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - No effect of acute tryptophan depletion on phosphodiesterase inhibition-related improvements of short-term object memory in male Wistar rats

AU - van Donkelaar, E.L.

AU - Prickaerts, J.

AU - Akkerman, S.

AU - Rutten, K.

AU - Steinbusch, Harry

AU - Blokland, A.

PY - 2013/8

Y1 - 2013/8

N2 - ObjectiveTo further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD). MethodWistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance. ResultsAlthough ATD significantly decreased TRP levels in the hippocampus 2h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed. ConclusionChanges in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.

AB - ObjectiveTo further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD). MethodWistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance. ResultsAlthough ATD significantly decreased TRP levels in the hippocampus 2h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed. ConclusionChanges in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.

KW - phosphodiesterase inhibitors

KW - acute tryptophan depletion

KW - serotonin

KW - rat object memory

KW - CEREBRAL-BLOOD-FLOW

KW - GELATIN-BASED MIXTURE

KW - NITRIC-OXIDE SYNTHASE

KW - AFFECTIVE BEHAVIOR

KW - SEROTONIN RELEASE

KW - AMINO-ACIDS

KW - BRAIN

KW - DOPAMINE

KW - CGMP

KW - NORADRENALINE

U2 - 10.1111/acps.12166

DO - 10.1111/acps.12166

M3 - Article

VL - 128

SP - 107

EP - 113

JO - Acta Psychiatrica Scandinavica

JF - Acta Psychiatrica Scandinavica

SN - 0001-690X

IS - 2

ER -